Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (39 page)
Other treatments target MS symptoms such as pain, tremor, bladder or bowel dysfunction, and fatigue.
“Up to 85 percent of MS patients have fatigue, and it may be the single most disabling symptom,” remarks Dr. Giesser. An antiviral medication called
amantadine
is widely used to treat MS-related fatigue.
Some patients benefit from a stimulant used for hyperactivity,
methylphe
nidate hydrochloride (Ritalin)
. Wakefulness promoting agents used for
sleep disorders,
modafinil (Provigil)
and
armodafinil (Nuvigil)
are also effective against MS-related fatigue. “Activating” antidepressants such as
fluoxetine (Prozac)
may also help fatigue.
Physical, occupational, and/or cognitive therapy may sometimes be recommended, and studies show aerobic exercise produces many physical and emotional benefits for MS patients, including improved bowel and bladder control and reduced fatigue.
Most MS patients are sensitive to increases in body heat, so exercising in an air-conditioned room is highly recommended. Dehydration can exacerbate fatigue, but many women with MS don’t drink enough water because of bladder incontinence. However, getting enough water during exercise is extremely important.
Antiseizure medications like
gabapentin (Neurontin)
and
carbamazepine (Tegretol)
help nerve pain. Other drugs used for MS-related pain include the tricyclic antidepressants
amitriptyline (Elavil)
and
imipramine (Tofranil)
, which interfere with pain signals from nerves, and a newer antidepressant,
duloxetine (Cymbalta)
, is also FDA indicated for pain. Antispasmodic drugs, such as
baclofen (Lioresal)
or
tizanidine (Zanaflex)
can help leg or back spasms. Prednisone may be given for optic neuritis.
MS patients have specific bladder problems. “In MS, the bladder often doesn’t store urine properly. So instead of holding a normal volume of urine, around two or three cups, before you have the urge to go or before you empty reflexively, a patient’s bladder may hold only a cup or so. The result is urgency, a spastic, nervous bladder that wants to go all the time,” says Dr. Giesser. “Or, MS patients may have a bladder that doesn’t empty itself completely, so when you void there’s still urine in the bladder, which leads to urinary tract infections, urine reflux (it can theoretically back up into the kidneys), and kidney disease. And there are women who have a ‘mixed’ bladder problem, a bladder that wants to empty all the time, but doesn’t empty well.”
For a purely spastic bladder that doesn’t store urine well, patients are prescribed
anticholinergic
agents, drugs that relax the bladder and allow it to hold more urine. In some cases, women are taught how to use urinary catheters. “For ‘mixed’ bladders we may use medication along with self-catheterization. It’s very individual.” A newer procedure,
sacral nerve stimulation
, a kind of “pacemaker” that helps eliminate abnormal nerve signals to the bladder, may work for some women with MS, she adds.
Another common problem is constipation. “Women who are less mobile are more prone to constipation. Some of the drugs we give cause constipation. A lot of women with bladder problems self-treat by restricting liquids and become dehydrated, which contributes to constipation. And MS probably has some effect on gut motility, as well,” says Dr. Giesser. In general, women with MS are advised to increase fiber intake, take bulking agents, keep well hydrated, and eliminate on a schedule to help keep regular.
Studies conducted by the National Multiple Sclerosis Society (NMSS) show that two out of three people with MS will remain ambulatory 20 years after diagnosis, and those numbers should improve as more people are treated earlier for the disease. Again, just because you’re not experiencing a relapse doesn’t mean there’s no disease progression. So medication is needed.
There is a great deal of research going on in MS, and many scientists are hopeful, especially about new drug treatments.
Among these new drugs is
Ocrelizumab
, which is being tested in relapsing MS. Late-stage trials show it is more effective than Rebif at reducing MS lesions in the brain, lessening relapses and the progression of disability. Ocrelizumab, a relative of rituximab, reduces the number of CD20-positive B cells, thought to be a key player in the myelin destruction.
35
Also in the pipeline is
Laquinimod
, a once-daily oral immunomodulator being tested for the treatment of RRMS. Laquinimod also increases levels of a molecule called brain-derived neurotrophic factor (BDNF), which may help protect nerves and myelin. In one large clinical trial, laquinimod significantly reduced atrophy of gray matter and white matter in the brain. Other large studies show laquinimod lessened relapses, disability, and problems walking for some patients.
7
Daclizumab
(also known as
Zenapax
) is an intravenous drug that’s also being studied in subcutaneous injections for RRMS and secondary-progressive MS. It’s a humanized monoclonal antibody (a “smart bomb” that zeros in on interleukin-2 receptors) and appears to inhibits disease activity by increasing the number of natural killer T cells (NK cells), autoreactive cells that play a key role in MS.
36
A large clinical trial comparing monthly infusions of daclizumab to weekly subcutaneous injections of Avonex showed daclizumab produced a 45 percent
reduction in relapses and reductions of around 60 percent in brain lesions. Risks associated with daclizumab treatment included infections, rash, and liver enzyme abnormalities. Side effects associated with daclizumab include respiratory and urinary tract infections, skin reactions, and elevated liver enzymes.
7
Some studies suggest that stem cell transplants might put many MS patients in long-term remission or even regrow myelin.
7
One technique,
hematopoietic stem-cell transplantation
(
HSCT
, see
page 142
) aspirates the patient’s own blood-forming cells from the bone marrow. First, the immune system is wiped out with high-dose chemotherapy (destroying the stem cells and the bone marrow), then the stem cells are infused back into the patient in hopes of “resetting” the entire immune system.
Another approach uses transplanted
mesenchymal stem cells (MSCs)
, which can be extracted from other tissues without the need to destroy the bone marrow. Animal studies indicate that, under the right conditions, MSCs can mature into myelin-producing cells, which may be a potential way to stop or even reverse myelin loss. In early clinical trials, MSC transplants had no major adverse side effects and showed some promise.
37
A third technique would harvest stem cells from bone marrow and infuse them back into cerebral spinal fluid, in hopes they will go into the central nervous system and perhaps help nerve cells regrow lost myelin.
Scientists are also investigating the possibility of using inactivated myelin-reactive T cells from a patient’s blood then injected back into the patient. The idea is that the body’s immune system may potentially protect the myelin. While it didn’t reduce brain lesions seen on MRI, in a one-year study the relapse rate was reduced among patients with a previous relapse who hadn’t been exposed to other MS therapies. In addition, “vaccine” treated patients remained relapse-free for a year. The vaccine, called
Tcelna
, is undergoing further study.
7
The American Academy of Neurology has endorsed plasma exchange (
plasmapheresis
) to treat severe exacerbations of relapsing-remitting MS. In plasma exchange the liquid part of your blood (the plasma) is replaced with plasma from a donor. In MS, plasma could contain immune factors that are attacking the myelin and nervous system. By swapping out the plasma, these factors are eliminated and symptoms of an MS flare may improve. It’s kind of like kidney dialysis in that it “cleans” the blood. Plasma exchange is an outpatient procedure, done in a hospital or outpatient facility, much like a
chemotherapy infusion. Each exchange can last two to four hours, and you may need two or three treatments a week for several weeks.
38
Ritonavir (Norvir)
, a drug used to treat
human immunodeficiency virus (HIV),
has shown potential benefits in preliminary animal studies. Ritonavir is a protease inhibitor, which affects an enzyme (called a proteasome enzyme) thought to play a role in the activation of lymphocytes that attack the myelin sheath in MS. Daily doses of ritonavir prevented clinical symptoms in the animal model of MS in such a way that researchers feel it may have a protective effect when given early in the disease. Drugs used in Alzheimer’s disease are also being tested to see whether they can slow cognitive decline in MS. Preliminary indications are that
donepezil (Aricept)
slightly improved cognitive function in the small group of patients who have tried it, Dr. Reder reports, but definitive data will have to come from large clinical trials. Newer drugs such as
galantamine (Reminyl)
may be even more effective.
Mariana’s story continues:
I was formally diagnosed when I was 30, when I started to have my first problems with walking. Then it was completely undeniable that I had MS, there was no way I could ignore it. I found myself a good neurologist . . . and my husband dragged me to my first support group, which scared me to death. Because there were a lot of people there who were worse off than I was. And that frightened me. I’d been told for years it could be MS. But I hadn’t accepted it in my mind until that point. I finally came to grips with it . . . I didn’t go back to the support group until later and I ended up being the program coordinator because I didn’t like the way it was being run; everyone would just sit around and complain. So we started getting people to come in to talk to us about MS and things to do to take charge of your life. And we also talked about touchy subjects like sexual dysfunction. For me, it was the emotional issues that were hardest. For example, it was hard to get my groceries in and out of the house and it was good to find out how to make that easier. But how does it make me feel as a person that I can’t do that anymore, that I have to ask neighbors to help me? That was the hardest part for me. To me, it’s a sign of weakness. You make yourself vulnerable and indebted to them. Some people like to do for others, do community service. But I had no way to “pay them back.” I felt very inadequate. That was an emotional stumbling block I had to get over.
While MS flares and relapses seem to be affected by hormones in younger women, there’s little research on the subject, and menopause is largely uncharted territory.
Women with MS often report that symptoms get worse in the days before their periods, but there have been only a few studies of this.
“We published the first abstract in 1990 on premenstrual fluctuations. We surveyed 149 women, who completed a questionnaire that asked, ‘Do you ever notice an increase in your symptoms during your menstrual cycle? If so, when?’ Seventy percent said they had changes in their symptoms every month, most of them saying this occurred during the week prior to menses,” said Dr. Giesser.
“About 40 percent noticed exacerbations—different than symptom fluctuation—came at a particular time during their cycle. Since then, there have been several other reports, self-report questionnaire samples that have also reported this. There have also been three small studies that reported some changes in MRIs correlated with different phases of the menstrual cycle. So we have uncontrolled, preliminary data in very small samples of women that yes, there seems to be an association with neurological symptoms and the premenstrual period. But we don’t know what is causing it.”
It’s not clear whether this is related to a temporary worsening of preexisting symptoms or disease exacerbation, comments Dr. Voskuhl. “These are very different. If you are getting a relapse, this could be an indication of inflammation and new demyelination. In contrast, when a woman is exposed to heat, her symptoms get worse, but it doesn’t mean her disease is worsening,” she points out. Menstrual changes fit best with a temporary worsening of symptoms, not a relapse of MS.
According to Dr. Giesser, the most common symptoms that worsen premenstrually are fatigue, imbalance, difficulty walking, and spasticity. Specific symptoms can be individually treated (see
page 307
). It’s not known whether there are menstrual cycle changes in the metabolism of various medications.
The good news is that MS doesn’t seem to hamper a woman’s ability to get pregnant and carry to term, and MS symptoms get better during pregnancy. Some studies suggest pregnancy may even slow the progression of the disease.
39
This is thought to be partly due to high estrogen levels (especially
estriol
), which appear to reduce immune system activity and reduce the frequency of MS attacks. The relapse rate seems to be lowest in the third trimester, and spikes in the three to six months after delivery as hormones return to normal levels (depending on whether or not a woman breast-feeds).
The American College of Obstetricians and Gynecologists (ACOG) reassures women with MS that they can “safely choose to become pregnant, give birth, and breastfeed children.”
40
A recent ACOG review notes there may be an increased risk of MS relapses after undergoing IVF or other assisted reproductive techniques, but “there does not appear to be a major increase in adverse outcomes in newborns of mothers with MS.”
40
This includes early miscarriage, stillbirth, birth defects and low-birthweight babies, says ACOG.
If you want to become pregnant, it’s advisable to discontinue any disease-modifying therapies under the supervision of your doctors. Since it may take longer to become pregnant, there’s a risk of relapse.
41
In this case, monthly intravenous steroids may be given (but only after a negative pregnancy test).
While pregnancy does have positive effects on MS, there’s no guarantee you’ll totally avoid a relapse. If your doctor feels there’s a high risk of relapse, ACOG says monthly
intravenous immunoglobulin (IVIG)
or steroids after the first trimester can be considered, although the safety data are limited.
40
And if your MS is severe or highly active, the risks of treatment have to be weighed with the still unknown risks to the baby.
The Multiple Sclerosis Association of America stresses that “because disease-modifying therapies (DMTs) are not tested in pregnant women, information about the potential risks of fetal exposure is not available to guide decision-making by women who are pregnant or wish to become pregnant.”
42
While recent data from a small number of women who became pregnant on MS drugs did not find abnormalities in their babies, this should not suggest that getting pregnant is considered safe while taking DMTs, says the MSAA.
The good news is that, for the most part, MS drugs are not needed because of pregnancy’s favorable effects. “Women should be off any one of these drugs for different periods of time depending upon the drugs’ metabolism before they try to get pregnant,” advises Dr. Giesser. “There are a lot of reports about women who happened to become pregnant while they were on these drugs, stopped the drugs, and had perfectly healthy babies. But we prefer to be cautious.”
During pregnancy, standard urine and blood tests are done to monitor for preeclampsia and other problems. A neurological exam would be given once or twice over the course of the pregnancy.
The decision on whether to resume disease-modifying therapy after delivery, especially if a woman is planning to breast-feed, is an individual one; a woman should discuss this with her neurologist, says Dr. Giesser. Because of a lack of safety data, Avonex, Betaseron, Copaxone, Rebif, and other interferon drugs can’t be used during breast-feeding.
Because the FDA has changed its labeling of medications during pregnancy and lactation (see
page 18
), check with your neurologist about specific MS drugs.
Aside from a spike in the relapse rate after delivery (as estrogen levels return to normal), women who breast-feed do not seem to have more relapses than women who don’t. “It’s not clear why there is a relapse rebound after delivery. It could be the effects of all the hormones returning to normal levels. All the immunosuppressant chemicals do, too. There’s an increase in prolactin during lactation, but I don’t think you can hang it on any one hormone,” says Dr. Giesser.
Some studies of women who exclusively breast-feed their babies suggest it may reduce the risk of relapses.
A German study presented at the triennial joint conference of ACTRIMS (Americas Committee for Treatment and Research in Multiple Sclerosis) and ECTRIMS (European Committee for Treatment and Research in MS) in 2014, found that women with MS who exclusively breast-fed their newborns for two months did not experience more postpartum relapses than those who bottle-fed or used supplemental feedings.
8
However, a 10-year study of all pregnancies at one Spanish hospital presented at the conference found no
difference in the course of MS between women who chose to breast-feed and those who bottle-fed their babies and restarted their treatment sooner.
7
If you choose to breast-feed, your doctor may prescribe monthly intravenous corticosteroids or IVIG to prevent relapses.
40
The biggest problem for many women who decide to become pregnant is fatigue and caring for their children in the event of a relapse. Strong support is needed from family members to share the load. To keep sleep disruption at a minimum, ACOG suggests scheduled naps during the day, pumping and storing breast milk on a schedule for others to feed to the baby while you nap. If you can, get outside help with household chores and consult your neurologist about potential relapse triggers.
Almost 20 percent of women experience postpartum depression (PPD) in the six months after giving birth. ACOG notes that women with MS may be at increased risk of PPD because of the increased incidence of depression in MS and possible worsening of symptoms.
40
It’s not known whether the wide shifts in hormones during perimenopause or the decline in estrogen after menopause affect the course of MS.
There’s also little information on the effects of menopause and hormone therapy on symptoms. A 2006 study found that 40 percent of women reported a worsening of MS symptoms at the time of menopause, 56 percent said they’d had no change, and 5 percent even reported an improvement.
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A study back in 1992 reported that 75 percent of women who used hormone therapy had an improvement in their symptoms.
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“A woman in her late forties or early fifties probably has had MS for 20 to 30 years, and she may stop having defined relapses as her disease becomes secondary progressive. So there are fewer relapses in menopause, but it may be for reasons that have nothing to do with hormones and more to do with the natural history of the disease,” remarks Dr. Giesser.
Menopause may have some effects on the symptoms of MS. For example, hot flashes raise body heat, which can worsen fatigue and other symptoms.
45
Menopause itself may not have any effect on the inflammatory process that underlies MS. However, there’s simply not enough information on the effect of hormone replacement on MS. “Right now, we have no data to suggest that
it’s good for them, although it may be, we certainly don’t have any data to suggest that it’s bad. So if a woman’s gynecologist or internist thinks she should be on hormone replacement for any kind of medical or gynecological reason, I tell them go ahead,” says Dr. Giesser.
Dr. Voskuhl concurs. “I think if a woman wants to take hormone replacement, there’s no reason not to. However, I don’t think very-low-dose estrogens will be very helpful.” Cooling vests can help dampen symptoms in hot weather and they may also be helpful to women experiencing hot flashes.
Some women may want to investigate branded herbal remedies like black cohosh (
Remifemin
) or red clover (
Promensil
) for menopausal symptoms.
Corticosteroids cause bone loss, but interferon drugs do not. So bone-building drugs are needed if a woman is taking steroids for MS attacks.
Throughout life, women are twice as likely as men to suffer from depression—and it’s also a more common symptom in people with MS. One small study found that the antidepressants known as
selective serotonin reuptake inhibitors (SSRIs)
not only help relieved depression, but also significantly reduce levels of gamma interferon. The researchers suggest that treating depression could also be an important factor in downregulating autoreactive T cells.
46
So it’s possible that treating depression may benefit women with MS.
Ana’s story, a postscript, 2015:
Developing MS is the toughest thing that has ever happened to me. I had to give up a 30-year career that I loved and that defined me. It utterly changed the assumptions about myself that I’d had my entire life—what my strengths are, how my brain works, and how I would live the rest of my life. My doctor said that none of his patients ever reconcile themselves to having this illness. And he’s right. I hate it.
That’s probably a healthy way to look at chronic illness. You have to think about those things that are important in your life and fight for them.
I was lucky to have access to aggressive treatment early on. It’s necessary to push for the best treatment and advice you can get, even if you have to travel for it. There is such a wide range of symptoms in MS that it’s important to find a doctor with lots of experience and many patients.
Because an illness like this is so isolating, volunteer work has become important to me. It gets me out with people, doing something of value, out of my own thoughts, and makes me use my brain.
I always said kiddingly that everyone with MS should have a dog (mine worked as a therapy dog). Having a dog is a social activity; you have to go out, walk, and you end up talking to people.
Most importantly, my life has found balance again. It has definitely changed. But there is life after diagnosis.
